Local transient myocardial liposomal gene transfer of inducible nitric oxide synthase does not aggravate myocardial function and fibrosis and leads to moderate neovascularization in chronic myocardial ischemia in pigs.

Details

Serval ID
serval:BIB_9A3E4FA195FC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Local transient myocardial liposomal gene transfer of inducible nitric oxide synthase does not aggravate myocardial function and fibrosis and leads to moderate neovascularization in chronic myocardial ischemia in pigs.
Journal
Microcirculation
Author(s)
Abegunewardene Nico, Schmidt Kai-Helge, Vosseler Markus, Dreher Michael, Keller Tandis, Hoffmann Nico, Vei Kerstin, Petersen Steffen E., Lehr Hans-Anton, Schreiber Laura M., Gori Tommaso, Horstick Georg, Muenzel Thomas
ISSN
1549-8719[electronic], 1073-9688[linking]
Publication state
Published
Issued date
2010
Volume
17
Number
1
Pages
69-78
Language
english
Abstract
Microcirculation (2010) 17, 69-78. doi: 10.1111/j.1549-8719.2010.00002.x Abstract Background: This study was designed to explore the effect of transient inducible nitric oxide synthase (iNOS) overexpression via cationic liposome-mediated gene transfer on cardiac function, fibrosis, and microvascular perfusion in a porcine model of chronic ischemia. Methods and Results: Chronic myocardial ischemia was induced using a minimally invasive model in 23 landrace pigs. Upon demonstration of heart failure, 10 animals were treated with liposome-mediated iNOS-gene-transfer by local intramyocardial injection and 13 animals received a sham procedure to serve as control. The efficacy of this iNOS-gene-transfer was demonstrated for up to 7 days by reverse transcriptase-polymerase chain reaction in preliminary studies. Four weeks after iNOS transfer, magnetic resonance imaging showed no effect of iNOS overexpression on cardiac contractility at rest and during dobutamine stress (resting ejection fraction: control 27%, iNOS 26%; P = ns). Late enhancement, infarct size, and the amount of fibrosis were similar between groups. Although perfusion and perfusion reserve in response to adenosine and dobutamine were not significantly modified by iNOS-transfer, both vessel number and diameter were significantly increased in the ischemic area in the iNOS-treated group versus control (point score: control 15.3, iNOS 34.7; P < 0.05). Conclusions: Our findings demonstrate that transient iNOS overexpression does not aggravate cardiac dysfunction or postischemic fibrosis, while potentially contributing to neovascularization in the chronically ischemic heart.
Keywords
Inducible Nitric Oxide Synthase, Gene Therapy, Angiogenesis, Heart Failure, Endothelial Growth-Factor, Heart-Failure, Induced Angiogenesis, Dysfunction, Overexpression, Expression, Infarction, Tissue, Mice, Microspheres
Pubmed
Web of science
Create date
24/02/2010 10:13
Last modification date
20/08/2019 15:01
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